Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling

Coronel-Oliveros, Carlos and Gónzalez Gómez, Raúl and Ranasinghe, Kamalini and Sainz-Ballesteros, Agustín and Legaz, Agustina and Fittipaldi, Sol and Cruzat, Josephine and Herzog, Rubén and Yener, Gorsev and Parra, Mario and Aguillon, David and Lopera, Francisco and Santamaria-Garcia, Hernando and Moguilner, Sebastián and Medel, Vicente and Orio, Patricio and Whelan, Robert and Tagliazucchi, Enzo and Prado, Pavel and Ibañez, Agustín (2024) Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 20 (5). pp. 3228-3250. ISSN 1552-5279 (https://doi.org/10.1002/alz.13788)

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Abstract

INTRODUCTION Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost-effective technique for studying dementia globally, but lacks mechanistic models and produces non-replicable results. METHODS We developed a generative whole-brain model that combines EEG source-level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls). RESULTS Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings. DISCUSSION The results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings.

ORCID iDs

Coronel-Oliveros, Carlos, Gónzalez Gómez, Raúl, Ranasinghe, Kamalini, Sainz-Ballesteros, Agustín, Legaz, Agustina, Fittipaldi, Sol, Cruzat, Josephine, Herzog, Rubén, Yener, Gorsev, Parra, Mario ORCID logoORCID: https://orcid.org/0000-0002-2412-648X, Aguillon, David, Lopera, Francisco, Santamaria-Garcia, Hernando, Moguilner, Sebastián, Medel, Vicente, Orio, Patricio, Whelan, Robert, Tagliazucchi, Enzo, Prado, Pavel and Ibañez, Agustín;
CORE (COnnecting REpositories)